Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.
Single Cell Genetic Profiling To Reveal Molecular And Cellular Changes In BRCA Preneoplastic Tissue
Funder
National Health and Medical Research Council
Funding Amount
$202,959.00
Summary
The initial molecular and cellular events that lead to breast cancer in women with BRCA1 or BRCA2 mutations are unknown. We will use state-of-the-art genomic tools (Single Cell RNA-seq and whole genome sequencing) to determine how cancer begins in absence of normal BRCA genes. Single cell genomic profiling of stem and daughter cells from pre-cancerous breast tissue will be used to identify early-indicator molecular changes that could be exploited in the clinic.
EphA3 Is A Marker Of Glioma Stem/progenitor Cells And A Potential Target For Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
EphA3 is a cell surface marker which is enriched on glioma ‘propagating’ stem cells (GSCs) and furthermore has a functional role in regulating GSC differentiation and fate determination. EphA3 therefore provides a novel therapeutic target for high-grade glioma.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.
How Does The Endometrium Regenerate? Role Of Epithelial Stem/progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$663,397.00
Summary
Endometriosis and endometrial cancer are disorders of endometrial growth and regeneration. We recently discovered adult stem cells in the endometrium (uterine lining), which are responsible for its regeneration each month during the menstrual cycle. We aim to examine the role of a molecular pathway in endometrial epithelial stem cell function during endometrial regeneration to identify novel targets for devising more effective non-hormonal therapies for endometriosis and endometrial cancer.
Mediator Kinase As A Therapeutic Target For Wnt/β-catenin Dependent Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$949,907.00
Summary
Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy ....Colorectal cancer is the third leading cause of cancer mortality in Australia and globally. The Wnt/?-catenin signalling pathway is a well established driver of colon cancer growth in >90% of cases. Using sophisticated genetic screens, we identified CDK8/19 as a colon cancer oncogene and critical regulator of Wnt/?-catenin activity. In this proposal, we will use innovative cancer models in mice and human cancer tissues to investigate newly developed CDK8/19 inhibitors for colon cancer therapy.Read moreRead less
Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.
A Preclinical Humanized Chimeric Model To Investigate Novel Therapeutic Strategies Against Breast Cancer Bone Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$696,362.00
Summary
Using the humanized in-vivo model presented, researchers are in a unique position to develop and evaluate novel therapeutic strategies against breast cancer bone metastasis at multiple intervention points from the primary tumour to bone metastasis. This model makes it possible to study anti-cancer and anti-resorptive effects of human-specific drugs such as the monoclonal antibody Denosumab. The model eventually may help to decrease morbidity and mortality of breast cancer patients.